The effect of myotonic dystrophy transcript levels and location on muscle differentiation.
In myotonic dystrophy type I (DM1), nuclear retention of mutant DMPK transcripts compromises muscle cell differentiation. Although several reports have identified molecular defects in myogenesis, it remains still unclear how exactly the retention of the mutant transcripts induces this defect. We have recently created a novel cellular model in which the mutant DMPK 3' UTR transcripts were released to the cytoplasm of myoblasts by using the WPRE genetic element. As a result, muscle cell differentiation was repaired. In this paper, this cellular model was further exploited to investigate the effect of the levels and location of the mutant transcripts on muscle differentiation. Results show that the levels of these transcripts were proportional to the inhibition of both the initial fusion of myoblasts and the maturity of myotubes. Moreover, the cytoplasmic export of the mutant RNAs to the cytoplasm caused less inhibition only in the initial fusion of myoblasts.
Mastroyiannopoulos
Nikolaos P
NP
The Cyprus Institute of Neurology & Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.
Chrysanthou
Elina
E
The Cyprus Institute of Neurology & Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.
Kyriakides
Tassos C
TC
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Uney
James B
JB
The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Dorothy Hodgkin Building, University of Bristol, Whitson Street, Bristol BS1 3NY, UK.
Mahadevan
Mani S
MS
Department of Pathology, University of Virginia, P.O. Box 800904, Charlottesville, VA 22908-0904, USA.
Phylactou
Leonidas A
LA
The Cyprus Institute of Neurology & Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus. Electronic address: laphylac@cing.ac.cy.
D020413:3' Untranslated Regions / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology*; D003593:Cytoplasm / Q000201:enzymology; D051379:Mice; D008954:Models, Biological; D024510:Muscle Development / Q000235:genetics*; D032446:Myoblasts / Q000166:cytology / Q000201:enzymology; D009223:Myotonic Dystrophy / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D050436:Regulatory Elements, Transcriptional; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; C585516:DMPK protein, mouse; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases